DESCRIPTION: The long term objective is to improve the dosimetry of bone during radionuclide cancer therapy through enhancements and use of small-scale dosimetry techniques. Radionuclide cancer therapy includes treatment with radiolabeled antibodies, radiolabeled compounds, and radionuclides. Approximately 125,000 cancer patients per year develop bone metastases in the U.S., and the severe pain, immobility, anorexia, and anxiety significantly impair the quality of life of these patients. Alternate radiopharmaceuticals are being studied for the treatment of primary and metastatic bone lesions that are less toxic than external beam radiotherapy. However, absorbed dose calculations to bone tissues require a degree of accuracy and an estimate of the associated uncertainties to carry out clinical studies with confidence. This is in order to correlate dose or dose distributions to bone tissues with toxicity and/or tumor control. The hypotheses of the proposed work are that: a) The existing bone dosimetric methods for use in radionuclide therapy can be enhanced by using small-scale dosimetry techniques that take into consideration the localized bone morphological characteristics and radionuclide distribution in bone tissues. b) These improvements will lead to a better understanding of normal-tissue toxicity and effectiveness of tumor control in clinical trials. To test these hypotheses, small-scale dosimetry techniques based on beta and alpha Monte Carlo transport will be used for the assessment of absorbed doses in localized bone regions. The dosimetric models will consider the morphological information obtained using histological images of human bones. Experiments using micro-thermoluminescent dosimeters will be carried out to validate the model predictions. A comprehensive study will be carried out to assess localized doses based on sources and target tissues using human bone specimens. Moreover, a digital autoradiography system for the quantitative spatial correlation of activity distributions in bone tissues will be assembled. This system will be used to assess the fractional activity distribution in animal models. Radionuclide distribution data from animal experiments will be used for extrapolation and correlation to human bones based on a comparative study of morphological and physiological parameters. Findings will allow experimental results obtained from these animals to be extrapolated to human bone with more confidence. Finally, a set of recommendations for the localized dosimetry of bone based on bone type and lesion will be established.